Vascular Smooth Muscle Cell Motility Is Mediated by a Physical and Functional Interaction of Ca2+/Calmodulin-dependent Protein Kinase IIδ2 and Fyn

• Published in: The Journal of biological chemistry 2013-10, Vol.288 (41), p.29703-29712
• Main Authors: Ginnan, Roman, Zou, Xiaojing, Pfleiderer, Paul J., Mercure, Melissa Z., Barroso, Margarida, Singer, Harold A.
• Format: Article
• Language: English
• Subjects: Animals; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Calcium/Calmodulin-dependent Protein Kinase (CaMK); Cell Migration; Cell Movement - drug effects; Cell Movement - genetics; Cell Movement - physiology; Cells, Cultured; Immunoblotting; Male; Microscopy, Confocal; Microscopy, Fluorescence; Muscle, Smooth, Vascular - cytology; Myocytes, Smooth Muscle - metabolism; Protein Binding; Protein Complexes; Protein Kinases; Proto-Oncogene Proteins c-fyn - antagonists & inhibitors; Proto-Oncogene Proteins c-fyn - genetics; Proto-Oncogene Proteins c-fyn - metabolism; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; RNA Interference; Signal Transduction; src-Family Kinases - antagonists & inhibitors; src-Family Kinases - genetics; src-Family Kinases - metabolism; Vascular Smooth Muscle Cells
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.477257

In vascular smooth muscle (VSM) cells, Ca2+/calmodulin-dependent protein kinase IIδ2 (CaMKIIδ2) activates non-receptor tyrosine kinases and EGF receptor, with a Src family kinase as a required intermediate. siRNA-mediated suppression of Fyn, a Src family kinase, inhibited VSM cell motility. Simultaneous suppression of both Fyn and CaMKIIδ2 was non-additive, suggesting coordinated regulation of cell motility. Confocal immunofluorescence microscopy indicated that CaMKIIδ2 and Fyn selectively (compared with Src) co-localized with the Golgi in quiescent cultured VSM cells. Stimulation with PDGF resulted in a rapid (